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Quan, P; Moinfar, F; Kufferath, I; Absenger, M; Kueznik, T; Denk, H; Zatloukal, K; Haybaeck, J.
Effects of targeting endometrial stromal sarcoma cells via histone deacetylase and PI3K/AKT/mTOR signaling.
Anticancer Res. 2014; 34(6):2883-2897
Web of Science PubMed

 

Autor/innen der Med Uni Graz:
Absenger-Novak Markus
Denk Helmut
Haybäck Johannes
Kolesnik Tatjana
Moinfar Farid
Quan Ping
Zatloukal Kurt
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Abstract:
Endometrial stromal sarcoma (ESS) is a rare gynecological mesenchymal malignancy with only few therapeutic options. This study aimed to investigate the efficacy of the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA) combined with inhibitors of the phosphoinositid-3-Kinase (PI3K) pathway in ESS therapy. The effects of SAHA combined with inhibitor of PI3K (LY294002, LY), mammalian target of rapamycin mTOR (rapamycin), and their combination on cell growth and the PI3K pathway in two ESS cell lines (ESS-1 and MES-SA) and one non-neoplastic cell line HESC, were investigated. SAHA reduced growth of the three cell lines by inhibiting protein kinase B AKT and mTOR/p70S6K cascade activation. SAHA combined with LY or rapamycin, or both, synergistically reduced p-p70S6K and p-4E-BP1 levels. SAHA combined with LY and rapamycin led to the strongest growth inhibition and slowest growth recovery among the combination treatments. SAHA combined with inhibition of PI3K and mTOR could represent an efficient therapy option for patients with ESS. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Adaptor Proteins, Signal Transducing - metabolism
Apoptosis - drug effects
Blotting, Western -
Cell Proliferation - drug effects
Endometrial Neoplasms - drug therapy
Endometrial Neoplasms - metabolism
Endometrial Neoplasms - pathology
Enzyme Inhibitors - pharmacology
Female -
Fluorescent Antibody Technique -
Histone Deacetylases - chemistry
Histone Deacetylases - metabolism
Humans -
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - metabolism
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - metabolism
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Sarcoma, Endometrial Stromal - drug therapy
Sarcoma, Endometrial Stromal - metabolism
Sarcoma, Endometrial Stromal - pathology
Signal Transduction - drug effects
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
Tumor Cells, Cultured -

Find related publications in this database (Keywords)
Endometrial stromal sarcoma
SAHA
PI3K/mTOR pathway
combination therapy
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